Heart failure in Parkinson's disease: analysis of the United States medicare current beneficiary survey.

OBJECTIVE: We sought to examine the prevalence of heart failure in elderly PD versus non-PD patients using a national sample of Medicare beneficiaries in the United States. SCOPE: The prevalence of heart failure in elderly PD patients was 2.27 times that of non-PD patients (19.4% versus 8.7%, 95% CI = 1.43-3.60, p 0.0005), and remained twice as high after excluding patients with stroke and possible vascular parkinsonism. CONCLUSIONS: In this cross-sectional study of a national Medicare database, heart failure occurred twice as frequently in elderly PD patients as in non-PD patients. Prospective studies are warranted to verify these findings.

Comparison of vessel dilator and long-acting natriuretic peptide in the treatment of congestive heart failure.

BACKGROUND: Long-acting natriuretic peptide (LANP; proANF 1-30) and vessel dilator (proANF 31-67) enhance sodium and water excretion in healthy human beings. The current investigation was designed to compare the beneficial effects of LANP and vessel dilator in persons with congestive heart failure (CHF). METHODS AND RESULTS: LANP and vessel dilator (100 ng/kg body weight/min, respectively) were given intravenously for 60 minutes to subjects with New York Heart Association class III CHF (n = 17) while their urine volume and sodium and potassium excretion were monitored. Vessel dilator increased urine flow more than 5-fold, which was still increased (P <.001) 3 hours after stopping its infusion. Vessel dilator enhanced sodium excretion 3-fold in subjects with CHF (P <.01), which was still significantly (P <.01) elevated 3 hours after infusion. The effects of LANP were diminished, with urine flow only increasing 2-fold (P <.05). The fractional excretion of sodium increased maximally 6-fold secondary to vessel dilator and 3-fold with LANP. The CHF control patients had no changes in the above parameters. Part of the diminished response to LANP was found to be caused by its rapid decrease in the circulation of individuals with CHF. CONCLUSIONS: These results indicate that vessel dilator has significant beneficial diuretic and natriuretic properties, which are not diminished, whereas the effects of LANP are diminished in human beings with CHF compared with healthy individuals.

Vessel dilator enhances sodium and water excretion and has beneficial hemodynamic effects in persons with congestive heart failure.

BACKGROUND: Vessel dilator, a 37-amino acid peptide hormone synthesized in the heart, enhances urine flow 4- to 12-fold and sodium excretion 3- to 6-fold in healthy humans. The present investigation was designed to determine whether vessel dilator might have similar beneficial effects in persons with congestive heart failure (CHF). METHODS AND RESULTS: Vessel dilator (100 ng/kg body weight per minute) given intravenously for 60 minutes to NYHA class III CHF subjects increased urine flow 2- to 13-fold, which was still increased (P<0.001) 3 hours after its infusion was stopped. Vessel dilator enhanced sodium excretion 3- to 4-fold in CHF subjects (P<0.01), which was still significantly (P<0.01) elevated 3 hours after infusion. Vessel dilator decreased systemic vascular resistance 24%, pulmonary vascular resistance 25%, pulmonary capillary wedge pressure 33%, and central venous pressure 27% while increasing cardiac output 34%, cardiac index 35%, and stroke volume index 24% without significantly affecting heart rate or pulmonary artery pressure in the CHF subjects. The control CHF patients did not have any changes in the above parameters. CONCLUSIONS: These results indicate that vessel dilator has significant beneficial diuretic, natriuretic, and hemodynamic properties in humans with congestive heart failure.

Noninvasive detection of allograft rejection in heart transplant recipients by use of Doppler tissue imaging.

BACKGROUND: Allograft rejection in heart transplant recipients is associated with lymphocytic extracellular infiltration and edema resulting in increased myocardial stiffness and abnormal relaxation. We hypothesize that these abnormalities will result in reduced myocardial relaxation velocities. Doppler tissue imaging is a novel noninvasive imaging modality that is capable of quantifying myocardial tissue velocities and may therefore be useful to identify allograft rejection. METHODS: In this observational study, 121 heart transplant recipients underwent pulsed-wave Doppler tissue imaging at the time of their surveillance endomyocardial biopsies. Peak relaxation and systolic velocities were measured from the inferior wall blinded to clinical biopsy. Biopsy results were classified as rejecting (3a, 3b, 4) or nonrejecting (0, 1a, 1b). RESULTS: The peak relaxation velocity in nonrejecting allograft recipients (n = 98) was 0.21 m/sec +/- 0.01. During moderate allograft rejection (n = 16), peak relaxation velocities decreased to 0.14 m/sec +/- 0.01 (p < 0.0001), and subsequently increased to 0.23 m/sec +/- 0.0 after successful treatment (p = 0.0001). Peak systolic velocities did not change during rejection, 0.08 m/sec +/- 0.02 when compared with nonrejecting recipients 0.09 +/- 0.02 (p = NS). With a cutoff value of less than 0.16 m/sec, the sensitivity of peak myocardial relaxation velocities for detection of rejection was 76%. The specificity and negative predictive values were 88% and 92%, respectively. CONCLUSION: Moderate allograft rejection results in reduced myocardial relaxation velocities, which can be detected noninvasively with pulsed-wave Doppler tissue imaging. Hence, Doppler tissue imaging is a useful noninvasive tool to exclude allograft rejection.

Effect of the calcium antagonist felodipine as supplementary vasodilator therapy in patients with chronic heart failure treated with enalapril: V-HeFT III. Vasodilator-Heart Failure Trial (V-HeFT) Study Group.

BACKGROUND: Despite therapy with diuretics, ACE inhibitors and digoxin morbidity and mortality in heart failure remain high and might respond favorably to an additional vasodilator. METHODS AND RESULTS: Male patients (n=450) with chronic heart failure (cardiac dysfunction and impaired exercise performance) on optimal current therapy (97% enalapril, 89% diuretics) were randomly assigned to double-blind treatment with felodipine extended release (5 mg BID) or placebo for 3 to 39 months (average, 18 months). Felodipine significantly reduced blood pressure and, at 3 months, increased ejection fraction (2.1% versus -0.1% units in the placebo group, P=.001) and reduced plasma atrial natriuretic peptide levels (-2.9 versus 26.9 pg/mL in the placebo group, P=.01) but did not improve exercise tolerance, quality of life, or the need for hospitalization. During long-term follow-up, the favorable effects on ejection fraction and atrial peptide did not persist, but felodipine prevented worsening exercise tolerance and quality of life. In the felodipine and placebo groups, mortality (13.8% versus 12.8%, respectively) and hospitalization (43% versus 42%) rates were similar, and a higher incidence of peripheral edema was the only apparent side effect of felodipine therapy. CONCLUSIONS: Felodipine exerts a well-tolerated additional sustained vasodilator effect in patients with heart failure treated with enalapril, but the only possible long-term benefit was a trend for better exercise tolerance and less depression of quality of life in the second year of treatment. The drug appears to be safe but not clearly efficacious in patients with heart failure.

Adrenomedullin, endothelin, neuropeptide Y, atrial, brain, and C-natriuretic prohormone peptides compared as early heart failure indicators.

OBJECTIVES: The present investigation was designed to determine the best endogenous plasma marker of early congestive heart failure (CHF). METHODS: Forty volunteers with mild CHF (New York Heart Association Class I, n = 12), moderate (Class II, n = 8), or severe (Class III and Class IV, each = n of 5) and 10 age-matched healthy individuals had the simultaneous evaluation of their respective plasma samples by the following radioimmunoassays: atrial natriuretic peptide, ANP; three N-terminal ANP prohormone assays, i.e., proANPs 1-30, 31-67, and 79-98 with the numbers referring to their amino acid (a.a.) sequences in their 126 a.a. prohormone; brain (BNP) and C-natriuretic peptides; N-terminal BNP prohormone; adrenomedullin; neuropeptide Y and endothelin. RESULTS: ProANPs 31-67, 1-30 and 79-98 had 100% (P = 0.01), 83% (P = 0.09) and 50% (P = 0.74) sensitivity in differentiating Class I CHF subjects from healthy subjects. The ANP, BNP, NT-proBNP, CNP, adrenomedullin, neuropeptide Y, and endothelin assays could not differentiate mild CHF subjects from healthy individuals. Logistic regression analysis revealed that only proANP 31-67 significantly (P = 0.0001) discriminated between early CHF (5226 +/- 377 pg/ml) and healthy individuals (1595 +/- 157 pg/ml). The positive and negative predicative values of proANP 31-67 were excellent (100% for each). The peptides measured in these assays were found to be independent markers of CHF with respect to left ventricular ejection fraction. CONCLUSIONS: ProANPs 31-67 is the most sensitive marker in discriminating NYHA Class I CHF subjects from healthy individuals. The ANP, BNP, NT-proBNP, CNP, adrenomedullin, neuropeptide Y and endothelin radioimmunoassays cannot discern mild CHF. These peptides are independent of left ventricular ejection fraction.

Risk factors for late recurrent rejection after heart transplantation: a multiinstitutional, multivariable analysis. Cardiac Transplant Research Database Group.

BACKGROUND: Previous studies of allograft rejection have focused on early episodes and risk factors from pretransplant variables. METHODS: This multiinstitutional study compared early (< 1 year) and late (> 1 year) rejection episodes and risk factors for recurrent rejection from variables both before and after transplantation among 1251 patients who underwent primary heart transplantation and available follow-up of greater than 1 year. RESULTS: There were a total of 1882 rejection episodes over a mean follow-up of 26 +/- 0.3 months. The hazard function (instantaneous risk per patient per month) peaked at 1 month followed by a low constant risk of rejection after 12 months. By multivariable analysis, the most dominant risk factors for recurrent rejection during the first posttransplantation year were a shorter time interval since transplantation and a shorter time since a previous rejection episode. Other factors included young age, female gender, female donor, positive cytomegalovirus serology, prior infections, and OKT3 induction. In contrast, after the first year, the dominant risk factors for rejection were a greater number of rejections during the first year and the presence of prior cytomegalovirus infections. CONCLUSIONS: These data show a striking time dependency for rejection episodes among heart transplant recipients. Factors that increase risk for rejection in the first year differ from risk factors for rejection in subsequent years. These data suggest that it may be possible to tailor rejection surveillance protocols and immunosuppression intensity, according to specific patient and time-related risk factors.

Normalization of circulating atrial natriuretic peptides in cardiac transplant recipients.

To assess whether heart transplantation (Htx) alters the marked elevation of circulating atrial natriuretic peptides usually found in patients with congestive heart failure (CHF), 14 subjects (nine with compensated and five with decompensated CHF), each with an ejection fraction < or = 28%, were evaluated. Immediately before and hourly for the first 12 hours after Htx, then daily for 21 days and every 1 to 4 weeks for 6 months, the circulating concentrations of the N-terminus (pro atrial natriuretic factor [ANF] 1-98), midportion of the N-terminus (pro ANF 31-67), and C-terminus (that is, ANF) of the 126 amino acid prohormone were measured. Increased (p < 0.001) levels of these peptides were found in superior vena cava, right atrial, and peripheral venous samples 1 hour after Htx in all subjects except one. The atrial natriuretic peptide levels correlated only with right atrial pressure (p < 0.01) in the first 24 hours. Circulating concentrations of these peptides returned to those of healthy adults between 5 and 12 days after Htx in 11 out of 14 Htx recipients. Thus successful Htx can restore the elevated circulating concentrations of atrial natriuretic peptides to those of healthy adults.

Prognostic significance of serial changes in left ventricular ejection fraction in patients with congestive heart failure. The V-HeFT VA Cooperative Studies Group.

BACKGROUND: In congestive heart failure patients, a single measurement of left ventricular ejection fraction (LVEF) provides important prognostic information. The importance, if any, of improvement or worsening in serial LVEF has not been defined. The Department of Veterans Affairs Cooperative Vasodilator-Heart Failure Trials (V-HeFT) data base was analyzed to determine the prognostic importance of LVEF changes. METHODS AND RESULTS: The data bases for V-HeFT I (n = 642) and V-HeFT II (n = 804) were analyzed. All patients had heart failure with documented exercise intolerance and abnormal LVEF or cardiac dilatation by chest x-ray or echocardiography. Radionuclide LVEF was obtained at baseline, within 6 months, and at least yearly after randomization to treatment. Cumulative survival subsequent to LVEF follow-up measurements was calculated for strata defined by LVEF change from baseline. In V-HeFT I, patients treated with hydralazine/isosorbide dinitrate (H-I) experienced a significant (p < 0.001) increase in LVEF and a survival advantage over those treated with placebo and prazosin. In V-HeFT II, both treatment groups showed significant improvements in LVEF, with the increase with H-I greater than that with enalapril, and enalapril provided a significant survival advantage over H-I. Change (> 5) in LVEF from baseline at 6 months (V-HeFT I) and 1 year (V-HeFT II) were the strongest predictors of mortality among the serial measurements and were significant after adjustment for therapy and baseline LVEF. Baseline clinical variables were not helpful in predicting the patients who would experience an improvement in LVEF. CONCLUSIONS: In patients with heart failure, serial measurements of LVEF provide additional important prognostic information. Vasodilator therapy with H-I is associated with an improvement in LVEF and prognosis. Vasodilator therapy with enalapril improves LVEF less than H-I but provides an additional survival benefit.

Mechanism of death in heart failure. The Vasodilator-Heart Failure Trials. The V-HeFT VA Cooperative Studies Group.

BACKGROUND: The Vasodilator-Heart Failure Trial (V-HeFT) data base provides information on the mechanism of death of male veterans entered into two trials that evaluated the effect of vasodilator therapy on survival in heart failure. METHODS AND RESULTS: Men aged 18-75 years with heart failure were recruited at 13 Department of Veterans Affairs Medical Centers. In V-HeFT I, 283 of 642 patients (44%) died during follow-up (average, 2.3 years), and in V-HeFT II, 285 of 804 randomized patients (35.5%) died during follow-up (average, 2.5 years). Mechanism of death was established centrally using a standardized classification. In V-HeFT I, 124 of the 283 deaths (43.8%) were sudden with no worsening of symptoms; in V-HeFT II, 104 of the 285 deaths (36.5%) were sudden. An average of 31.5% of the deaths (31.4% and 31.6%, respectively) in the two trials was due to pump failure. The proportion of sudden deaths that occurred without worsening of symptoms was similar in patients with and without ischemic heart failure. Sudden deaths tended to occur earlier and pump failure deaths later in both V-HeFT studies. There was a trend for a lower percentage of cardiac deaths from pump failure and a higher percentage from sudden death in subgroups with higher peak exercise oxygen consumption (VO2), higher ejection fraction, and lower plasma norepinephrine levels. The proportion of deaths that occurred suddenly was similar in placebo, prazosin, and hydralazine plus isosorbide dinitrate treatment groups but was significantly lower in the enalapril treatment group. In V-HeFT I, measures of cardiac function and VO2 predicted pump failure death and sudden death. In V-HeFT II, VO2 and cardiothoracic ratio were independent predictors of all-cause deaths and pump failure deaths; only ejection fraction was an independent predictor of both pump failure and sudden death. CONCLUSION: Although mechanistically distinct terminal events can be identified in patients with heart failure and physiological measurements can provide some insight into the risk of these disparate events, sudden death and pump failure death both appear largely to be linked to the severity of cardiac dysfunction and symptoms. Strategies to identify individuals for selective preventive therapy are not yet practical.

Enalapril decreases prevalence of ventricular tachycardia in patients with chronic congestive heart failure. The V-HeFT II VA Cooperative Studies Group.

BACKGROUND: Patients with heart failure have a high prevalence of serious arrhythmias and sudden cardiac-death. METHODS AND RESULTS: Male patients aged 18-75 years with chronic heart failure were randomized to enalapril or hydralazine-isosorbide dinitrate. Short-term (4-hour to 8-hour) Holter tape recordings were performed before randomization, at 3 months, at 1 year, and yearly thereafter. Of 804 patients randomized to therapy, 715 had Holters at baseline. Couplets were noted in 56% versus 60% and ventricular tachycardia (VT) (three or more consecutive ventricular premature beats) in 27% versus 29% of patients randomized to enalapril versus hydralazine-isosorbide dinitrate, respectively. The presence of VT at 3 months, 1 year, and 2 years predicted significantly higher mortality during the subsequent year (p < 0.0001, p < 0.001, and p < 0.037, respectively). In the enalapril group, VT prevalence decreased by 27% at 1 year (p < 0.02). A decrease in prevalence of VT was not seen in the hydralazine-isosorbide dinitrate group. New VT was seen in 11% of enalapril patients versus 24% of hydralazine-isosorbide dinitrate patients at 1 year (p < 0.002). When compared with hydralazine-isosorbide dinitrate at 1 and 2 years, there was a 52% and 49% reduction, respectively, in sudden deaths in the enalapril group. Thus, at 1 and 2 years, the decrease in sudden deaths in the enalapril group coincided with the decrease in VT prevalence and the decrease in new VT emergence. CONCLUSIONS: In patients with heart failure, VT and couplets predict increased mortality. When compared with hydralazine-isosorbide dinitrate, enalapril decreases both the persistence of baseline VT at 3 months and the emergence of new VT at 1 and 2 years. The reduction in VT prevalence parallels a reduction in sudden death. The effect of enalapril on survival over hydralazine-isosorbide dinitrate may be related to its ability to reduce prevalence of ventricular arrhythmia.

Pretransplantation risk factors for acute rejection after heart transplantation: a multiinstitutional study. The Transplant Cardiologists Research Database Group.

To better understand the phenomenon of acute rejection in the current era of heart transplantation, complete rejection data (918 rejection episodes) from 25 institutions were analyzed for all 911 patients undergoing primary heart transplantation between January 1, 1990, and July 1, 1991. During a mean follow-up of 8.1 months (maximum, 18 months), 54% of the patients had one or more rejection episodes. The mean cumulative number of rejection episodes per patient was 0.8 at 3 months, 1.10 at 6 months, and 1.3 at 12 months after transplantation. By univariate analysis, female donor hearts (irrespective of recipient sex) (p < 0.01) and the use of induction therapy (p < 0.01) were associated with greater cumulative rejection frequency. By multivariate analysis, younger donor age and female donor gender were risk factors for earlier rejection. Solution of the multivariate equation predicted an 85% probability of rejection at 1 month for a 5-year-old female with a female donor and 50% for a 50-year-old man with a male donor. Inferences: (1) In the current era, over 40% of patients appear to be free of rejection during the first year after transplantation. (2) Younger recipient age and female donors are associated with earlier onset of allograft rejection, but the precise immunologic basis for these observations remains unknown. (3) In this experience, induction therapy did not delay the onset of first rejection nor did it reduce the cumulative number of rejection episodes. Further studies are indicated to examine the need for induction therapy.

Effect of diuretic therapy on the electrocardiographic response to exercise.

For nearly 30 years clinicians have assumed that diuretic therapy, per se, even in the absence of clinical hypokalemia, can cause false-positive exercise ST-segment responses. The precept has stubbornly persisted in the literature and in the day-to-day interpretation of exercise tests in clinical settings. The assumption probably originated with very early studies of patients on diuretics, in which other causes of false-positive tests were not excluded. This study was undertaken to show that diuretic therapy alone is not sufficient to cause ST depression. Twenty healthy male volunteers, aged 18 to 35, with normal history and physical examinations, echocardiograms, electrocardiograms, serum electrolytes, renal function tests and exercise tests, took 50 mg of hydrochlorothiazide daily for four weeks. Exercise tests, serum electrolytes, and renal function tests were repeated at Weeks 2 and 4. The administration of the diuretic resulted in a statistically significant reduction in serum potassium (from 4.37 +/- 0.37 to 3.96 +/- 0.28, and 3.94 +/- 0.31 mEq/l at 2 and 4 weeks, respectively). There were no abnormal ST-segment shifts on any of the exercise tests. It is concluded that exercise-induced ST-segment shifts in otherwise healthy young male normokalemic subjects who are taking diuretics should not be ascribed to a false-positive response to diuretics.

Spinal epidural hematoma causing cord compression after tissue plasminogen activator and heparin therapy.

Bleeding is the most serious complication of thrombolytic therapy and limits its usefulness. We have reported a case of epidural hematoma, a rare occurrence after combined therapy with tissue plasminogen activator (TPA) and heparin. We emphasize that in patients treated with thrombolytic agents, any trauma may increase the risk of bleeding. The sudden onset of back pain and neurologic deficits should alert the clinician to the possibility of spinal hematoma with cord compression.

[Cardiology in rural areas]. / Cardiología en la ruralia.

Based on a personal experience after having established a cardiology clinic in the town of Arroyo (Puerto Rico), we analyzed the patient population served and the services that were rendered. After collecting the data from the clinical files, we were able to obtain information on diagnosis, follow-up, diagnostic test and therapeutic procedures performed. In general, it was found that only a minority of patients needed long term cardiology follow-up and specialized diagnostic or therapeutic interventions. In conclusion we established that the presence of a cardiology clinic in the rural areas is reasonable, if their function remains as merely consultative.

[Heart transplant: development and maturity of the program at the University of South Florida and the General Hospital of Tampa]. / El trasplante cardíaco: desarrollo y madurez del programa en la Universidad del Sur de la Florida y el Hospital General de Tampa.

Cardiac transplantation has evolved from an experimental procedure to an accepted mode of therapy that prolongs life in patients with severe heart failure. The University of South Florida-Tampa General Hospital began performing cardiac transplantation for the treatment of end-stage cardiac disease in June 1985. Since then, 50 heart transplantations have been performed and 37 patients are alive and well. The one-year actuarial survival is 78% and the two-year actuarial survival is 72%. Multiple complications have been encountered, most notably rejection and infection. The recent approval of the USF/TGH program as a Medicare funded cardiac transplantation center is expected to greatly expand the number of potential recipients and will provide the residents of Florida, the Southeastern United States and the Caribbean with an additional health care resource.

Cardiac transplantation: University of South Florida--Tampa General Hospital experience.

Cardiac transplantation has evolved from an experimental procedure to an accepted mode of therapy that prolongs life in patients with severe heart failure. The University of South Florida-Tampa General Hospital began performing cardiac transplantation for the treatment of end-stage cardiac disease in June 1985. Since then 42 heart transplantations have been performed and 30 patients are alive and well. The one-year actuarial survival is 78.73% and the two-year actuarial survival is 72.15%. Multiple complications have been encountered most notably rejection and infection. The recent approval of the USF/TGH program as a Medicare funded cardiac transplantation center is expected to greatly expand the number of potential recipients and will provide the residents of Florida, and the Southeastern United States, with an additional health care resource.